Development of cirrhosis, as defined by imaging criteria [ Time Frame: Five years ] [ Designated as safety issue: No ]

The primary objective of this prospective longitudinal study is to determine the utility of abdominal ultrasound (US) at enrollment to predict the development of cirrhosis in subjects with cystic fibrosis (CF) within a five year period.

Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis

Official Title ICMJE

Prediction by Ultrasound of the Risk of Hepatic Cirrhosis in Cystic Fibrosis (PUSH)

Brief Summary

The specific aims for this study are:

To determine if sonographic findings predict the risk of progression of liver disease to cirrhosis by comparing cystic fibrosis subjects with heterogeneous echogenicity pattern on ultrasound to those with normal echogenicity pattern on ultrasound

To develop a database and biorepository of serum, plasma, urine and DNA to aid the investigations in ascertaining the mechanisms, consequences, genetic risk factors and biomarkers for the development of cirrhosis

To determine if there are differences in health related quality of life, pulmonary or nutritional status in children with cystic fibrosis who have a heterogeneous echo pattern on ultrasound compared to those who have a normal echo pattern on ultrasound

To determine if Doppler velocity measurements of hepatic and splenic vessels predict an increased risk for the development of cirrhosis.

To determine if cirrhosis on ultrasound progresses to portal hypertension during the study period

To determine if homogeneous liver progresses to either cirrhosis or heterogeneous liver.

Detailed Description

For subjects in longitudinal follow up, this study will:

Collect detailed clinical and demographic information about each subject at enrollment and during follow up,

Obtain and store imaging data from the subject at entry and during follow up,

Obtain and store serum, plasma and urine samples from the subject at entry (after matching) and during follow up,

Obtain and store DNA from the subject,

Obtain and store DNA from the biological parents,

Obtain and store quality of life data from the subject and parents at enrollment and during follow up

Study Type ICMJE

Observational

Study Design ICMJE

Observational Model: CohortTime Perspective: Prospective

Target Follow-Up Duration

Not Provided

Biospecimen

Retention: Samples With DNA

Description:

During this study, blood and urine specimens will be obtained, de-identified and shipped to and stored at the NIDDK repositories for use in future CFLD ancillary studies. This "biobanking" is a critical aspect of this longitudinal study to facilitate the creation of a resource of DNA and other specimens from a meaningful number of patients with CFLD. In addition, obtaining and storing DNA or EBV-transformed leukocytes (from which DNA can be extracted) will allow future studies to investigate genetic causes and influences (modifier genes) in CFLD.

Sampling Method

Non-Probability Sample

Study Population

The study population will consist of males and females 3 through 12 years of age with Cystic Fibrosis and pancreatic insufficiency who are enrolled in the CFF or Toronto CF registry studies. All racial and ethnic groups will be included.

Condition ICMJE

Cystic Fibrosis

Pancreatic Insufficiency

Intervention ICMJE

Procedure: Abdominal Ultrasound

To establish eligibility and/or markers regarding echo pattern types.

Other Name: Doppler Ultrasound

Other: Sample collection procedures

Samples of urine, serum, plasma, and blood for DNA from children and blood for DNA from parents will be requested from participating subjects

Other Name: Doppler Ultrasound

Study Group/Cohort (s)

Group A

Approximately 60 subjects with a heterogeneous echo pattern of the liver on abdominal ultrasound (HTG US).

Interventions:

Procedure: Abdominal Ultrasound

Other: Sample collection procedures

Group B

Approximately 680 subjects with a normal echo pattern on abdominal ultrasound (NL US). Of these subjects, approximately 110 will be matched 1:1 with Group A participants and followed for the duration of the study. The remaining unmatched subjects will not be followed beyond their initial visit.

Interventions:

Procedure: Abdominal Ultrasound

Other: Sample collection procedures

Group C

An estimated 30 subjects with cirrhosis pattern on abdominal ultrasound. These subjects will be followed in the study.

Interventions:

Procedure: Abdominal Ultrasound

Other: Sample collection procedures

Group D

An estimated 30 subjects with diffusely homogeneous echogenic pattern at screening ultrasound will be followed in the study.

Interventions:

Procedure: Abdominal Ultrasound

Other: Sample collection procedures

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.